Therapeutic uses of pungent botanicals and their related compounds

ABSTRACT

A new class of general antiinfective agents extracted from pepper, ginger, and other plant species containing vanillyl and piperidine ring structures typical of the pungent principal found in pepper and ginger. The role of these structures, their attached hydrocarbons groups, and other agents found with the plant extract is demonstrated in the topical treatment of dermatophyte infections, tissue injuries, and abnormal proliferations of keratin.

This application is a 371 of PCT/US93/4763 filed May 19, 1993.

TECHNICAL FIELD

The invention relates to a new class of general antiinfective compoundsobtainable from plant species of the pepper, and ginger families, andchemically related species that are also useful in the treatment oftissue injury, and skin disorders.

BACKGROUND ART

There is a wide array of microorganisms that are pathogenic to man, andother organisms. Pathogenic bacteria, viruses, rickettsia, and fungi maycause disease in their host organism whether plant, animal, or man.

Fungal diseases of man and animals, often referred to as mycoses, may beclassified into two broad categories. Deep tissue, or systemic mycosesinvolves the wide dissemination of pathogenic fungi growing in internalorgans, and tissue, and superficial mycoses, which generally representdifferent types of pathogenic fungi than those that infect the skin,hair, nails and mucosa.

Deep tissue mycoses including aspergillosis, actinomycosis,blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis,nocardiosis, paracoccidioidomycosis, entomophthoromycosis andoccasionally candida, may infect the lungs, brain, bones, spinal fluid,liver, heart, kidneys, and other internal organs, as well as the skin.Depending on severity, deep tissue mycoses may cause illness that rangesfrom asymptomatic to life threatening.

Superficial mycoses, also called dermatophytosis, describe disorderssuch as ringworm, athlete's foot, favus and candida, which infect theskin, hair, nails and mucosal linings. There are perhaps three dozen orso known species of pathogenic fungi, and yeasts responsible for causingthese diseases.

The National Health Survey of 1971-1974 projected from its sampling thatabout one out of every twelve people in the United States had some formof dermatophytosis, with men being four times more likely than women tocontract infections.

Surveys of other nations reveal a much higher incidence of superficialmycotic diseases, among the poor, and underdeveloped countries ofAfrica, Asia, South America, and those areas of the world havingtropical climates.

Tinea is another term used to describe ringworm. It is usually followedby another term which describes the particular location of theinfection. Hence, athletes foot is often referred to as "tinea pedis".Scalp ringworm is also known as "tinea capitis"; body ringworm as "tineacorporis", jock itch as "tinea cruris" etc. Though not considered to belife threatening, as some deep tissues mycoses can be, superficialmycoses assuredly take a fair toll of man and animals in misery,inconvenience, and expense.

Though not classified as a serious illness by the medical profession,this does not necessarily reflect the view point of those sufferers ofsuperficial fungal infections. On a personal level, an athlete whoseperformance on the playing field is diminished because of painful cutson the feet due to an athlete's foot infection, may consider it to be aserious illness.

A young woman who develops bald patches on her scalp due to ringworm mayfeel that she has a serious illness. It is also likely that she may feelthe same about a ringworm infection of the fingernails, where the nailsassume a horrible, unsightly appearance as a result of thickening,brittleness and discoloration typical of the disease. Add to this a yearand a half of systemic treatment to see results, and she may feel thatshe indeed has a very serious illness.

Do people who are unemployed, low income, or without medical coverageconsider an illness, that in addition to causing discomfort, can costthem several hundred dollars a year in treatments, and still not becured? Do ranchers think of ringworm as a serious disease, when the feedlots, who are paying high prices for livestock, refuse their herdbecause of ringworm? I think the answer is a resounding "yes!."

Antibiotic drugs such as penicillin, tetracycline, and sulfa ect.,though often effective in the treatment of bacterial infections, areuseless against infections caused by viruses, rickettsia, and fungi.Fungal disorders, for example require treatment with a separate group ofantimicrobial drugs, known as antifungals, or antimycotics.

Antimycotic drugs (FIGS. 14-16) were first introduced in the 1950's withnystatin (1954), amphotericin B (1958), and griseofulyin (1959). Thesedrugs were originally administered systemically. Tolnaftate (FIG. 17)was introduced in 1965 as the first effective topical antifungaltreatment. Since the 1970's, a number of "azole" derivative antifungalssuch as clotimazole (FIG. 20), miconazole (FIG. 21), econazole (FIG.22), ketoconazole, and others have made their appearance as antimycoticsfor both systemic, and topical administration. The more current trendhas been toward the developement of a "triazole" (FIG. 23) class ofantifungals, including such derivatives as fluconazole (FIG. 24),terconazole (FIG. 25), and itraconazole ect.

Prior art treatments for superficial mycoses, in addition to beingexpensive, require repeated application before improvement can be seenin the patient. Currently available over the counter treatments,containing clotrimazole, miconazole, tolnaftate, or undecylenic acid,recommend up to sixty applications of the product in order to providefull benefit. More treatments are often required.

Regardless of economic impact, even wealthy individuals, with the besthealth care available suffer with all the others when it comes to thediscomfort, and bother of repeated application of medication that isslow acting, and often ineffective at producing cure or relief ofsymptoms.

Even prescription topical antifungals, administered by a dermatologist,may require as many as two hundred applications over a period of threemonths to cure some cases of athlete's foot alone. Nail infections mayrequire eighteen months of multiple, daily treatment to provide cure. Inaddition to being very expensive and time consuming, applying themedicine repeatedly each day is bothersome. Coupled with the discomfortof the fungal disorder, the expense, and inconvenience associated withthe treatment adds further to the misery of the condition.

The current cost of treating ringworm and other superficial mycosesexcludes the economically disadvantaged, who suffer most from thecondition, from receiving treatment. Poor sanitation, a lower standardof general health, along with the fact that it is rarely treated, addsto the greater prevalence of ringworm, and other superficial mycosesamong lower income individuals. To a low income family in the UnitedStates, an extra five dollars a week expense to buy the cheaper topicalover the counter fungal treatments can cause real hardship on thehousehold budget. For the disadvantaged of many developing countries,five dollars a week looks more like a good wage for a healthy workingman supporting a family, than what one can afford to pay to treat a skincondition that takes weeks to cure, if it can be cured at all. For thesereasons, superficial mycoses among the poor usually go untreated, beingprohibitive because of the cost of treatment.

In this respect, the current array of prior art antifungal treatmentshave failed to significantly heal superficial mycoses throughout theworld, being inaccessible to most of the world because of cost. Inaddition to the misfortune of not having viable treatment for tens ofmillions of sufferers of fungal infection, no markets are created, andno products sold, to the advantage of no one. Prior art antifungaltreatments keep the price of treatment high, the market volume small,and undiverse, and only bring marginal relief to a relative few of themany suffers.

The bad economics of currently available topical antifungals prohibitstheir use in the livestock industry, as well. The cost of the medicine,coupled with the labor required for repeated application to livestock,forbids the creation of a significant market for these medicines withinthe industry. As stated earlier, livestock infected with ringworm arerefused by feed lots. The rancher holding them back, in turn, raises hisprices to cover this liability; effecting all processors and consumersof meat products.

Ringworm, being highly contagious, can spread through a herd within afew short weeks, not allowing enough time for treatment and recovery inthe weeks prior to going to market, even if they are treated. With thecurrent way of topical antifungals, treating food animals for ringwormis an absurd notion. The cost involved in applying a medicine, perhapsfifty times, to a single head of livestock could never be justified. Forthis reason, treatment is withheld, to the disadvantage of both therancher and the animal, which in addition to suffering discomfort,spreads the disease to other animals, perpetuating the cycle further. Inaddition to money lost, no viable solution is offered by pharmaceuticalmanufacturers which would otherwise enjoy a new, very large potentialmarket.

Whether or not one feels the economic impact of superficial mycoses, allsuffers experience the inconvenience of having to make repeatedapplication of currently available prior art topicals. The necessity ofmaking repeated applications is an indication of weak drug action, andthat is another great flaw of prior art antifungal treatments.

Systemic antifungal drugs are also used to treat superficial mycoses, inaddition to the deep tissue diseases. Drugs like amphotericin B,clotrimazole, enconazole, griseofluvin, ketoconazole, miconazole, andnystatin, are administered internally, usually orally, or by injection.Like the topical antifungals described earlier, most of the systemicstreatments require multiple doses in order to be effective. Systemictreatments are the most costly of all, requiring the supervision of aphysician. They are most dangerous to the patient, with undesirable sideeffects that can further endanger the health of the patient. The risk ofdamage to internal organs, and adverse reactions to other medications,are factors that must be carefully weighed by physicians administeringsystemic antifungals. With this, other less severe, yet unpleasant sideeffects, include nausea, vomiting, headache, dizziness, fever, diarrhea,and many other adverse effects that contribute to the misery and illhealth of the patient.

Amphotericin B (FIG. 14), given by injection in the treatment ofsystemic fungal infection, carries with it the risk of liver and kidneydamage, and can also result in blood disorders. It interacts negativelywith many cardiac medications, and diuretics, as well as otherantibiotics.

Griseofulyin (FIG. 16), usually taken orally, for fungal infections ofthe skin, hair, and nails, has a risk of liver damage. Reduced bonemarrow function, with lowered white cell levels is another possibleadverse effect of treatment. Drug interactions with anticoagulants, andbarbiturates reduce effectiveness, and the risk to pregnancy oftenforbids treatment.

Ketoconazole, taken orally for systemic fungal infections, also carriesthe risk of liver damage as a result of treatment. The effectiveness ofketoconazole is diminished by interaction with various antacids, andother gastric medications. Ketoconazole increases the potency of otherdrugs, and is reduced in potency by some antibiotics.

Miconazole (FIG. 21), taken by injection for fungal infection of thelungs, brain, kidney, and lymph nodes, can alter blood chemistryresulting in anemia. Miconazole also interacts negatively withmedications for diabetes, epilepsy and anticoagulants. The effectivenessof amphotericin B is reduced by miconazole.

Nystatin (FIG. 15), taken orally for candida disorders, is of little usein the treatment of systemic fungal infections. Though having far feweradverse side effects than the other antifungal drugs, it is ineffectiveagainst most fungal infections except candida, and aspergillus, makingit of limited usage.

Treatment with these systemic antifungals often produces many other veryunpleasant side effects, in addition to the adverse effects upon bloodcomposition, internal organs and other medications being taken by thepatient. Taken internally, amphotericin B, griseofulyin, ketoconazole,miconazole and nystatin, may cause nausea, vomiting, diarrhea,dizziness, headache, fever and other disorders during the coarse oftreatment. These symptoms, though unpleasant enough for the patient, canalso lead to more serious complications, further advancing the illhealth of the patient. Beside these known adverse effects, others yetunknown, will be discovered with further research. The full effect ofinternal treatment with antibiotics on the body is a very complexmatter, and warranting much caution.

Topical treatment of superficial mycoses is much safer than internaltreatments. The prior art, however, has failed to produce topicalantifungal medications effective enough to deal with more seriousinfections. This necessitates the use of systemic treatments, which aremore dangerous, costly, time consuming, and associated with many otherunpleasant illnesses to treat even superficial mycoses.

The adverse effects of prior art systemic antifungal treatments is amore serious complication of treatment for deep tissue mycoses thansuperficial mycoses. Patients suffering from deep tissue disorders, suchas cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis,paracoccidioidomycoses, and others, are generally in a much poorer stateof health than patients being treated for dermatophytosis. For thisreason, the adverse effects of systemic treatment have greater impact onthe overall health of patients being treated for deep tissue mycoses.This is of particular significance in the treatment of immunocomprimisedpatients.

Deep tissue mycoses find their greatest opportunity in immunocomprimisedpatients. These include cancer, organ transplant patients, and others onimmunosuppressant medication, and particularly with patients sufferingfrom immune disorders such as acquired immune deficiency syndrome,otherwise known as AIDS. These patients, who are very ill indeed, arehighly susceptible to infection from these diseases, as their naturaldefenses against the pathogenic microbes is greatly reduced.

The adverse effects of treatment with currently available prior artsystemic antifungals, are devastating to immunocomprimised patients, tothe point of being themselves life threatening to the patient- To thosepatients in greatest need of treatment for deep tissue mycoses, themedication is most dangerous to administer.

With the steady rise in treatment with immunosuppressant drugs, and themuch more dramatic rise in the number of cancer, and AIDS casesreported, and anticipated for the future, the demand for safe,effective, and low cost treatments for both deep tissue, and superficialmycoses, is more urgent than ever. The prior art has largely failed tomeet this criteria as a result of high cost, low ineffectiveness, andthe high toxicity of their antifungal medications.

The focus of the prior art upon the development of azole derivatives, isperhaps largely responsible for keeping the cost high, and theeffectiveness of antifungal treatments so low. The newer generationtriazole (FIG. 23) derivatives, including fluconazole (FIG. 24),terconazole (FIG. 25), itraconazole, and others, cost many millions ofdollars to develop, and apparently are not that much more effective thanthe prior generation imidiazole (FIG. 19) derivatives, and certainly aredoing nothing to make treatment more affordable, or convenient. Besidethis, they have much narrower application than the imidiazoles, and areconsidered auxiliary, and not mainline treatments.

It seems doubtful at this point, that either of the azole groups willproduce derivatives of significantly greater effectiveness in thetreatment of fungal disorders, than what is currently available withprior art treatments.

DISCLOSURE OF INVENTION

Accordingly, several objects and advantages of my invention include amethod for treating fungal infections, otherwise known as mycoses, inwhich cure is complete with as few as one single application of mymedication. Rather than making scores of applications, usually requiredby prior art antifungal medications, my medication usually requires justone treatment to affect full cure. The effectiveness of my medication isnothing short of astounding, and is truly generations ahead of currentlyavailable antifungals.

I have discovered that plants of the pepper family, and plant specieswith similar chemistry contain active agents that provide complete curewhen applied to areas infected with mycotic diseases. These agents maybe administered in the wide range of commonly used drug vehicles andcarriers, with results that are absolutely unprecedented when comparedto prior art treatments.

Tinea, in its various forms, otherwise known as athlete's foot, jockitch, favus, and ringworm, along with other types of dermatomycoses suchas candida, may be completely healed after a single treatment with mymedication. Topical treatment of these diseases, in the form of aninfusion, bath, douche, shampoo, lotion, drops, tincture, plaster,powder, aerosol, or other carriers, all provide outstanding results.

Currently available prior art over the counter topical treatments forringworm containing clotrimazole, miconazole, tolnaftate, or undecylenicacid, usually require several weeks of daily multiple treatments beforeimprovement can be observed in the condition. In addition to theconsiderable expense of having to buy several containers of themedication, the time, and inconvenience involved in making repeatedapplications with meager results adds further to the misery anddiscomfort of the disease. Even mild to moderate cases of tinea caneasily require more than sixty applications of these products before thecondition improves. The weak therapeutic action of these prior art, overthe counter treatments is often insufficient to produce adequateresults, and must be treated by a physician, using prescription topical,and systemic antifungals taken internally.

Prescription treatment with antifungal medications is the most expensiveof all treatments. Beside the cost of having an attending dermatologist,the medications themselves are more expensive than the over the countervarieties. This type of treatment, being the best the prior art has tooffer, still may require several months of multiple daily doses of theantifungal medication to cure some kinds of ringworm. Treatment forathlete's foot may require up to three months of multiple daily doses ofthe medicine before the condition can be cured. Ringworm infections ofthe toe nails can take up to eighteen months to heal! So adding theexpense of visits to a dermatologist, time lost from work or leisure,the time and inconvenience of applying the medicine, the cost of themedicine, and the ongoing discomfort of the disorder, all have aneconomic impact that is quite considerable, in addition to thediscomfort of both the disease and the side effects of treatment.

Systemic treatment with antifungal drugs, such as amphotericin B,clotrimazole, griseofulyin, ketoconazole, miconazole, nystatin andothers, in addition to being expensive and time consuming, have many badside effects that can further endanger the health of the patient. Thesedrugs, taken internally, carry the risk of damage to liver and otherinternal organs, and adverse effects upon blood chemistry. Patientsreceiving such treatments must be monitored for changes in blood andorgan function, as a safeguard against serious damage that can resultfrom treatment. Prior art systemic antifungals also interact adverselywith a large number of other medications, another area that requiresclose attention by the attending physician. Beside this, other adverseeffects include nausea, vomiting, diarrhea, fever, headache, and otherunpleasant symptoms that accompany the discomfort of the disease.

With my medication, a single topical application is all that is usuallyrequired to completely cure most types of dermatophytosis. Evenrecalcitrant cases of athlete's foot are healed in as few as half adozen doses of my medicine. Body and scalp ringworm lesions disappear,usually within the first day after treatment, and require no follow updosages. With my treatment, systemic treatment of superficial mycoses isa thing of the past. Instead of making several visits to adermatologist, and taking repeated doses of drugs that are expensive,dangerous, slow acting, and create other illnesses as a side effect, oneneed only make a single, or few topical applications of my treatment forcomplete cure. In addition to effectiveness that is truly astounding,these pepper compounds are completely safe, being derived from commonlyconsumed food. Topical applications of my treatment generally requireless active agents, than what might be commonly consumed in a meal thatincludes any of the pepper species. In addition to that, there is nolong term, chronic exposure to the medicine, as is required with priorart topical antifungals, that have only a long term therapeutic effect,if any at all!

The prophylactic action of pepper constituents continues to protectdamaged tissue from reinfection, by maintaining its antifungal actionfor days after treatment, in addition to it's direct, and immediatefungicidal action. This further aids rapid healing, by allowing diseasedtissue to regenerate, rather than concentrate energy on combatingdisease

Pepper also appears to act as an immunostimulant, by precipitatingleukocytes, and other mononuclear cells, along with a variety ofantifungal compounds from the blood, and surrounding tissue, to the areaof infection. Though done primarily through inducing inflamation, painand discomfort are not required in order to receive the full therapeuticbenefit. Pepper compounds are also believed to aid in the delivery ofthese antifungal immune resposes of the body, and increase their potencyin addition to its own antifungal actions.

Healing, and excellerated regeneration of diseased tissue is anotherimportant therapeutic action opepper compounds. While whole, healthyskin is the best protection against infection from dermatophytes,pepper's ability to regenerate diseased skin is equally astounding toit's antifungal action.

The healing, and tissue regeneration actions are further demonstrated inthe treatment of other forms of dermatitis such as dandruff, seborrhea,eczema, warts, corns ect. These chronic skin disorders, which are notcurrently recognized as being of microbial origin, also respond withcomplete cure when treated with pepper compounds, often in the same wayas superficial mycoses. These diseases, for which the prior art believesincurable, may also be completely cured with my invention, often aseasily as superficial mycoses such as ringworm are cured.

In a study of eight patients, all infected with various forms ofdermatophytosis, complete cure is obtained after one topical applicationof the medication of the current invention in five of the eight casesstudied. The other three cases studied are cured within half a dozentreatments or less. None of the patients are taking any kind ofmedication for ringworm, or for any other disorder, and no specialsterilization measures of clothing, furniture or bedding are taken,beyond otherwise good personal hygiene.

In the first portion of the study, a family of three, all afflicted withringworm, are completely healed after a single topical treatment with apepper compound.

The infant has developed approximately six ringworm lesions about theback of the scalp, and back, and right side of the neck. The first fewlesions were noticed a month before.

The mother of the infant has about six ringworm lesions on the rightarm, most on the outside bicep. The appearance of the lesions was firstnoticed approximately three months before.

The father of the infant has approximately eight ringworm lesions on theleft arm, most on the outside bicep. The right arm has four lesions,also on the outside of the bicep. Four other lesions appear on theshoulders, and lower back. The man first noticed lesions of this typeapproximately eight years earlier.

On all three subjects, the ringworm lesions have the same generalappearance. The lesions are ring shaped, with slightly raised outerborders that are sometimes crusty. The lesions are red, with a smooth,and sometimes scaly interior. A clear, sticky fluid sometimes covers thelesion. The average diameter of the ring is about 15 mm (0.6"), withsome as large as 20 mm (0.8"). The lesions appear, and remain forseveral weeks, sometimes disappearing, leaving lighter colored skin atthe site of the prior lesion.

The man is first to be treated with a preparation of capsicum, wherein aplaster is applied to three lesions on the left bicep. A very slight,momentary tingling sensation is reported. The sensation lasts for aboutthe first five minutes after application, and is not uncomfortable. Theplaster is left on the skin for about one hour, then rinsed off withwater. Afterward, the lesions appear redder than they did prior toapplication of plaster. After six hours, the lesions appear to bewhiter, with the coloration being more similar to the skin tone of thehealthy skin, than prior to treatment. At twenty hours, all threelesions appear healed, as it requires very close examination to revealthe site of the prior lesion. The characteristic patch of lightercolored skin that normally accompany lesions that have healed bythemselves is not present.

The other dozen or so lesions found on the man are examined, and foundto be substantially unchanged from their last examination the daybefore. Another examination on the third day yields the same results,with no sign of the three lesions that were treated and healed, andlittle change in the untreated lesions.

Also, on the third day after initial treatment, the other dozen ringwormlesions on the arms and trunk of the man, are treated with the samecapsicum plaster, with identical results. All twelve lesions, regardlessof location, are healed with the exact location of the prior lesionbeing difficult to determine because of the advanced degree of healingof the skin in that area.

One week later, the woman is treated with the same capsicum plaster asthe man, with similar results. At three days after treatment, all sixlesions are completely healed in similar fashion to those on the man.

One week after the woman is treated, the infant girl is also treatedwith the capsicum plaster in the same manner as both her parents, and ishealed in the same way, with the disappearance of all lesions withinabout one day. It is also interesting to note that the infant girldisplays no sign of discomfort when the medication is applied, and doesnot cry, or even appear to take notice of the treatment.

Regular examinations of these three patients, over a period of severalmonths, fails to identify the reappearance of one single ringworm lesionin any one of them. Each lesion of the patient is completely healed ofringworm, after just one single topical treatment with my medicine. 100%cure of twenty-eight lesions on three subjects is accomplished after asingle dose of my medication, without reappearance of a single lesion.This is done without sterilization measures, and aside from any othermedication whatever.

In another portion of the study, a woman in her middle thirties ishealed of athlete's foot within hours of a single treatment of mymedication. The woman works a full time job, in which she is required tobe on her feet most of the time. Approximately one week after havingpurchased a more comfortable pair of shoes for work, the woman developsan inflammatory variety of athlete's foot. The primary symptoms areintense itching on top of the toes and foot, felt mostly in bed atnight, along with a bad, musty foot odor. The itching is now interferingwith sleep each night.

The woman soaks her feet in a bath, prepared from infusion of capsicum,for fifteen minutes. The woman reports a warm, tingling sensation thatlasts about ten minutes. This treatment is administered at 8:00 p.m. Thewoman retires for the evening at 10:00, and does not experience any ofthe itching characteristics of the previous evenings. For three weeksthe woman reports not a single recurrence of the itching on the feet.She continues to wear the same footwear as before, and does not take anykind of sanitary, or other precautions to avoid reinfection.

After about three weeks, the woman begins to notice a gradual return ofthe itching on top of the feet that she had experienced before. Withinanother week or two, the itching is as intense as ever, and is againinterfering with sleep.

The woman's feet are treated with a lotion of capsicum, using raw aloevera gel as the lotion carrier. Lotion is applied to the feet, andrinsed off with water at the end of half an hour. The treatment isadministered at 8:00 in the evening, before the woman retires for theevening at 10:00. The woman reports no itching that evening, norafterwards, for many months. She disposes of the comfortable shoes, shehad bought for work, and has no further recurrence of athlete's footsymptoms. The woman is completely healed of athlete's foot after justone single treatment with my medication!

The sixth case involves a five year old girl, who is completely healedof a recalcitrant case of dry athlete's foot. Prior to treatment, thechild's feet are peeling severely in the areas between the toes, and onthe entire sole of the foot. Loose skin, in pieces as large as about 4mm (1/8") square are hanging around the lower edge of the ball of thefoot. The entire sole of the foot is calloused, and has a wrinkledappearance. Deep cuts occur periodically on the ball of the foot andaround the base of the toes, particularly the great and small toes. Thechild often complains that her feet hurt from the cuts, but otherwisedescribes no other discomfort or symptoms. The girl has had thesesymptoms for about three years, since age two years.

At age two years, the girl develops a particular affection for a certainpair of shoes, and wears them constantly, refusing to wear other shoes.Weeks later, the girl develops a very offensive foot odor. Afterward,her feet gradually develop the symptoms described above, becomingchronic over the next three years.

An ethanol tincture of capsicum is applied to the girl's feet. The girlcomplains about a stinging sensation in the cuts around her great andsmall toes. The girl cries for about five or ten minutes, then reportsthat the sting is gone. The girl is also treated with the same capsicumtincture on days three and five, after the initial treatment. Theinvestigator performs these second and third treatments because he isnot sure if the first treatment is sufficient to penetrate such thickcallouses on the soles of the feet, having never treated such badlydamaged skin with this particular treatment. On day three, just prior tothe second treatment, the feet are examined and appear slightlyimproved. The cuts around the toes have formed scabs, and no discomfortis reported by the girl after application of the tincture.

On day five, the feet are again examined before receiving the thirdtreatment, and again appear to be further improved. The cuts arecontinuing to scab over and heal, and the girl reports no discomfortfrom the medicine. This general trend continues for the next severaldays, yet treatment is not again administered.

By the fourteenth day, the feet are nearly, completely healed. There areno cuts or scabbed cuts, and no pealing or loose skin. The callouses arenearly, completely reduced, and the skin has a healthy color andtexture, and no longer has a wrinkled, ragged appearance. It is notpossible to determine that the girl has ever had athlete's foot, as herfeet are healthy and normal. The child is excited that her feet are"like new again".

On day twenty one, the girl's feet are again examined. The skin aroundthe bottom and sides of the toes has succumbed to reinfection, as theskin is again peeling, though not as severely as before the firsttreatment.

At six weeks, the girl's feet have returned to the pretreatmentcondition. The skin on the sole of the feet is thickened and calloused.The skin on the soles and between the toes is peeling and has a raggedappearance. Cuts appear periodically at the base of the toes, on theheel and at the ball of the foot. The dry athlete's foot is back in fullforce.

The reinfection of the girl's feet is not presumed to be the result ofrecontamination, as no sanitary measures have been taken to preventreinfection, and the girl continues to wear the same footwear as beforethe treatment. As these pathogenic fungi find opportunity in damagedskin tissue such as that described, the skin must be healed to preventreinfection. The best protection from reinfection being healthy,undamaged skin.

This is one reason why the prior art has such difficulty curing thistype of ringworm. The therapeutic action of prior art antifungals is soweak and slow acting, it arrests the resident fungi only enough to allowthe healing process of the skin a slight advantage.

This is why a case of dry athlete's foot can easily require twelve weeksof daily, multiple treatments with prior art medications to providecure, which is usually only temporary.

The dramatic improvement of the girl's feet between the last treatmenton day five, and the examination on day fourteen, suggests acceleratedhealing over any activity of fungi during this interval. It alsosuggests a prophylactic action by my medicine that may provideprotection for perhaps seven days or more.

Recalling complete cure after a single dose of my medicine in the firstfive cases leads to the conclusion that the fungi are eradicated oninitial contact with my medication. What distinguishes them from thissixth case is the relatively minor degree of skin damage they suffered,in relation to the present case. This further supports the notion of theprophylactic action of my medicine, as seven days or less is ample timeto heal the minor skin damage caused by the body ringworm lesions.

In an attempt to determine the maximum duration of capsicum'sprophylactic effect, and to compare it's performance with that ofsynthetic capsaicin, the synthetic version of the primary irritant foundwithin natural capsicum, the girl's feet are again treated.

Prior to treatment, the girl's feet have again returned to theiroriginal, recalcitrant condition that was noted prior to the firsttreatment. The girl's feet are peeling severely on the bottom and sidesof the toes, and on the ball of the foot. The skin in this area isthickened, and calloused, with deep cracks sometimes resulting inpainful cuts. The skin has a wrinkled, dry, and ragged appearance, withintermittent red blotches, occupying about half the total surface area.Small cuts appear periodically around the base of the great and smalltoes, which often cause pain, especially when walking.

A lotion of capsicum, consisting of 4 cm³ (1/4 teaspoon) of ground redpepper mixed with 48 cm³ (12 teaspoons) of raw, aloe vera gel, isapplied to the child's left foot. The girl describes a ticklingsensation as lotion is being applied, and is laughing. About threeminutes afterward, the girl begins crying, saying that the cuts on hertoes are burning. She continues to cry for about ten more minutes, andafterward indicates that the burning has gone.

At the same time, an ointment of capsaicin, consisting of about 0.03percent capsaicin (from oleoresin) in turpentine oil is applied to theright foot. There are no cuts on the right foot at this time, and thegirl reports no discomfort from the medication.

The medications described above are applied once each week for the nexttwo weeks, and observed regularly over the next three weeks, with littlenotable change the first few days.

On day three, the feet are examined, and appear to be showing signs ofimprovement. The peeling does not seem as severe, and the red blotcheslook as if they are fading. The cuts on the left foot are healing, andshow no sensitivity when firmly squeezed with the fingers.

On day four, the feet are again examined, and look much better than theprevious day. The peeling is again reduced, and the red blotches havecompletely disappeared. The right foot looks slightly better than theleft, suggesting the therapeutic effectiveness of the capsaicinointment. The cuts on the left foot show further progress in healing.

Upon examination on the sixth day after treatment, the child's feet lookvery much improved. The loose skin has for the most part worn away,being replaced by healthy skin that shows no scaling, or discolor. Thecuts on the left foot have disappeared, and both feet show reduced skinthickness, and only faint reminder of cracks that are mostly healed.Both feet look about the same, suggesting equivalent therapeuticperformance between capsicum and capsaicin preparation.

The examination of day seven reveals little change in the condition ofthe feet from day six except that they appeared slightly better on daysix. Small cuts along the base of the small toe on the right foot arenot causing discomfort, as the medicine is applied for the second time.

Subsequent examinations of the next seven days reveal a similar patternto that of the prior week. Little change is observed the first few daysafter treatment, with very noticeable improvement being observed betweenthe fourth and sixth day after treatment. This pattern is alsoestablished on days eleven through thirteen, yet without substantialadvance in the stage of healing beyond that observed on the sixth day.

It is evident that a single weekly application of my medicine producessubstantial improvement in recalcitrant cases of athlete's foot. Thoughthis improvement is sustained, it is not usually sufficient to inducefull cure, at least within a three week span. Nor does the degree ofimprovement compare to the results of the prior study, in which themedication was applied three times within the first week. Depending uponthe case, two to four applications per week should be sufficient toprovide complete, and sustained cure for recalcitrant cases of athlete'sfoot.

To demonstrate a complete cure for recalcitrant athlete's foot, and tocompare the performance of a red pepper (capsicum frutescens) extractwith that of one made from black pepper (piper nigrum), the girl's feetare again treated. The girl's right foot is treated with an ethanoltincture of capsicum made from ground red pepper, while the left foot isat the same time treated with a similar tincture prepared instead withan equal amount of black pepper. The girl's feet are treated eleventimes, once every other day, over a period of three weeks. The patternof previous tests is also observed in this trial, with both the red, andblack pepper tinctures performing with equal effectiveness. As in theother tests with the girl, significant improvement is observed betweenthe fourth, and sixth day after treatment, with dramatic improvementbeing noted at two weeks. At three weeks, very little sign of the priordisorder remains, and the condition does not return after weeks ofobservation. The girl is healed of recalcitrant athlete's foot, withjust eleven topical treatments over a period of less than three weeks.

In the seventh case study, a woman of sixty is cured of a dry variety ofathlete's foot. Prior to treatment, the woman's feet have peeling skinbetween the toes, and thickened soles with cuts on the underside of theheal.

The woman's feet are soaked in a capsicum tea for fifteen minutes at atime, once a day, for five days. On the second day, the woman complainsthat her feet are very dry, and that one of the cuts on her heel ismaking walking difficult because of the pain. By the fourth day, sheindicates the cessation of those symptoms. After eight weeks, the feetare examined and the skin appears healthy, with no sign of peeling orthickening of the skin. The woman indicates that after the fourth day oftreatment, she did notice the reimmergence of symptoms at the time ofthe eight week examination, and felt cured since.

In the eighth case study, a boy of thirteen is completely healed of asevere fungal infection of the face, and neck after just two weeks oftreatment with my medication.

Over a period of nearly five months, the boy has been suffering fromwhat is described as an angry, bright red rash about the face, frombeneath the eyes, down to the bottom, and sides of the neck. The boy'sfather describes the disorder as "literally eating his son's face away."The boy, and his family are for some time quite distressed, as treatmentadministered by a general practitioner, and two dermatologists over morethan four months, fails to heal the condition. The expense of treatmentis nearing $1,000 out of pocket. The visits to the physician, have costthe parents more than twenty hours away from work, and the boy must beexcused from school the same amount of time. The boy is of coarse doublydistressed, as in addition to the discomfort of the disease, he mustbear the humiliation of wearing this rash on his face that is morehorrible in appearance than a severe case of acne!

A skin scraping sent to a laboratory reveals the presents of fungalhyphae, not of the ringworm variety.

The boy is given griseofulyin orally, but must discontinue treatmentafter one week as a result of severe nausea. The boy is then giventolnaftate topically, and has shown no significant improvement in thecondition over a period of several weeks.

The boy is then given lotion prepared with capsicum, and instructed toapply the medication once every other day after bathing until symptomsdisappear. All other treatments are also discontinued.

The boy's father administers the treatment as prescribed, and is seeingnoticeable improvement by the third day. The condition continues toimprove over this period, and by the tenth day the skin is almostcompletely healed, with barely a remanent of the prior diseaseremaining. To say the least, the boy's family and friends are amazed,and astounded at the rapidity of cure of this horribly unsightlycondition, that had persisted for so many months before withoutimprovement, often referring to the medicine as "a literal Godsend!"

The treatment is discontinued after only two weeks, and the boy ishealed without relapse after many weeks of observation even until thetime of this writing.

As can be seen from these several examples, the effectiveness of mytopical antifungal medication is truly astounding. Single applicationcure of dermatophytosis, being unheard of among prior art treatments, isthe usual result with the medication of my invention. No longer is itnecessary for suffers to endure prescription therapies, which are slowacting, time consuming, expensive and potentially dangerous with manyother unpleasant adverse effects. With my medication, embodied in theform of a topical, over the counter treatment, even recalcitrant casesof athlete's foot can be cured with a few periodic applications of mymedicine. Instead of months of antibiotic therapy, administered by adermatologist, the sufferer can cure the condition themselves, with asafe, inexpensive and astonishingly power medicine, such as mine.

The savings in health care cost that my invention provides for thetreatment of dermatophytosis alone is astronomical. Prior arttreatments, that cost many hundreds of dollars and representconsiderable loss of time from work and leisure, are no longer required.With my medication, these same disorders can be cured for pennies, withonly minutes of time required by the sufferer, and without the attentionof a physician.

With the very considerable cost savings my medicine provides, thesufferer also gets prompt relief from the symptoms of dermatophytosis.Instead of waiting days, or weeks to gain relief from ringworm itch, asis the requirement of prior art topicals, my treatment provides reliefin just minutes! Instead of enduring weeks, or months of systemicantifungal treatment to see improvement in a recalcitrant case ofathlete's foot, with my treatment, dramatic improvement is seen withinhours, to a few days of the first treatment. The savings here, in termsof human discomfort and inconvenience is incalcuable.

The amazing healing power of my medicine, coupled with tremendouseconomic advantage it provides, opens the doorway for the creation ofmany new, and very large markets for topical treatment of superficialmycoses. Rather than exclude the economically disadvantaged from aviable treatment, as prior art antifungals do because of their highcost, and lack of effectiveness, my treatment can be produced and soldat a very low price relative to prior art topicals, and still provide avery large profit margin for marketers. My product will greatly expandthe market base for ringworm medicines, by tens of millions ofindividuals worldwide, and most important, provide effective medicalcare for those in greatest need of it. Severe cases of ringworm can becompletely cured for less than a penny in actual cost of the activeagents within my medication. If such a product is sold for a dollar, itwould open the market up to many millions of people world wide, andprovide a tremendous commercial opportunity for drug manufacturers.

In the United States, a topical ringworm treatment, such as mine, costsless to produce than the current prior art over the counter brands, yet,is scores times more effective. If sold at competitive prices to priorart brands, the superior effectiveness of my medication will radicallyoutsell the competitor brands. The high effectiveness of my treatmentwill also attract the purchase of low income individuals, who otherwiseare not able to afford prior art medications. Because of the need topurchase several containers of prior art over the counter topicaltreatments to cause even temporary cure, of a single case, low incomepeople do not buy the medication because of the cost, and simply gountreated. In addition to adding more misery to their alreadyunfortunate circumstances, it further contributes to the spread of thedisease, thereby perpetuating this undesireable cycle.

Prior art topical treatments for dermatophytosis, such as clotrimazole,miconozale, tolnaftate, and undecylenic acid, are not effective fordealing with the problem. Their weak drug action, coupled with theirhigh prices, preclude their use among the economically disadvantaged andhave not been able to establish a market for them.

The expense and weak action of prior art antifungals has also occludedcreation of a market for treatment of ringworm, and other superficialmycoses within the livestock industry. The current economics of treatingfood animals for ringworm, with available prior art treatments, forbidsthe practice. The economic impact of ringworm within the livestockindustry is felt first by the rancher, whose head are refused by thefeed lot because of it. Being highly contagious, and finding particularopportunity under certain weather conditions, an outbreak of ringwormcan infest a herd within a very short amount of time, and prevent themfrom market. This economic liability is then added to the cost of thefood product, which eventually impacts everyone. Ringworm and othersuperficial mycoses are just another business liability, for which priorart treatments have failed to remedy, much less establish a market for.

With the treatment of the current invention, the combination ofunprecedented effectiveness, and lower cost, make it now economicallyfeasible to establish a product for treatment of ringworm, candida, andother superficial mycoses, within the livestock industry. My medicationis especially appropriate for this application, being itself derivedfrom food compounds, generally recognized as safe (GRAS) by the U.S.Food and Drug Administration. With my medicine, an outbreak of ringwormamong a herd of livestock within the last week before market, need nolonger prevent them from market as before.

The astonishing effectiveness of my medicine, in comparison to prior arttopical and systemic antifungals, has crucial bearing in the treatmentof deep tissue, as well as, superficial mycoses. The commoninterchangability of currently prescribed prior art medications betweentopical and systemic administration, suggests the use of my inventionfor systemic treatment of deep tissue mycoses as well. As prior artantifungals, such as amphotericin B, econazole, griseofulyin,ketoconazole, miconazole, nystatin, and related drugs are administeredas systemics, as well as topicals, my treatment shows excellent promiseas a systemic antifungal, as well as a topical.

The active principals found within capsicum, and piper species, andrelated families provide an important research tool in the systemictreatment of deep tissue mycoses, such as aspergilliosis, actinomycosis,nocardiosis, cryptococcosis, histoplasmosis, blastomycosis,coccidioidomycosis, paracoccidioidomycosis, entomophthoromycosis,candidiasis, and others. Pepper extracts may be given by injection intothe blood, spinal fluid, or directly into diseased tissue. Analogs ofthese active constituents may be developed for oral administration,however, some modification of the molecular structure may be required toprevent decomposition of the active agents that occur as a result ofdigestive processes.

With the very rapid increase in the incidence of deep tissue fungaldisorders, and projections suggesting even greater increases for thefuture, the need for more powerful, safer treatments is more crucialthan ever. Finding opportunity in immunocomprimised patients such ascancer, organ transplant patients, and others on immunosuppressantdrugs, and those suffering from AIDS: these diseases are lifethreatening. Also life threatening to these patients is systemicantifungal treatment with prior art medicines. Their high toxicity, andmultiple adverse side effects, often have devastating impact on thehealth of these patients, who are already very sick. Complicationsarising from treatment with prior art antifungals can end their life, inaddition to adding additional misery to their already tragiccircumstances.

Even immunocompetent patients can become very ill as an adverse effectof systemic antifungal treatment. Serious adverse effects include damageto liver, kidneys, and other internal organs. Changes in bloodcomposition often lead to enemia. Less serious adverse effects, yet onesthat are capable of causing considerable misery for the patient includenausea, vomiting, diarrhea, dizziness, headache, fever and otherdisorders. These adverse effects are hard enough to bear for anotherwise healthy patient being treated for athlete's foot, let alone apatient having just undergone an organ transplant, or in the advancedstages of AIDS, or cancer!

Pepper, on the other hand, being itself a food compound consumed by man,is good for the body, not harmful as the prior art antifungals can be.All of mankind, throughout the world has used these plants for food, andfrom long experience of thousands of years, knows them to be safe andhealthful to the body. Pepper compounds, being far less toxic than priorart antifungals, will not induce further illness in the patient, likeprior art treatment, as dosages are usually less than the amountscommonly eaten at one time by those who enjoy the fruit, or spice.

Solanacea, piperacea, and related species of plants are widespreadthroughout the world, and are grown in virtually every country of theworld. Their active constituents have all been synthesized, and some canbe obtained very cheaply from existing commercial sources. Pepperextracts are versatile, and work very well in all conventional drugvehicles and carriers, allowing for the maximum amount of productembodiments.

Today, more than every before, the importance of having medications thatare not only safe, and effective, but cost effective as well, isbecoming critical to the preservation of our very way of life. Theescalating cost of health care in the United States is causing realhardship on the middle and lower economic classes to the extent thatabout 1 in 6 americans cannot even afford health care insurance.

Health care costs are consuming a greater share of the middle classbudget with each new year. Money that would otherwise be spent on betterhousing, college educations, early retirement, entertainment, and manyconsumer goods must instead be spent to cover the cost of health care.In addition to lowering the standard of living for our citizens, ittakes much needed capital away from many key industries that provideemployment for our citizens and create tax revenues that pay thenational debt, and support our government.

Rising health care costs have excluding our lower income citizens fromadequate medical care, and are the primary contributor to the nationaldebt. They are moving this country, and others closer, and closer towardeconomic ruin, while excluding increasingly larger segments of oursociety from adequate health care. How is a society benefitted by asystem that provides adequate health care at the cost of economic ruin?At best, that is merely trading one illness for another, i.e., aphysical illness for an economic one.

A medication, such as put forth by the current invention, counters thistrend of escalating health care costs being economically, as well asmedically therapeutic. It is very safe, and of unprecedentedeffectiveness. It provides far more complete, and rapid cure of diseasethan prior art medications, and at a cost of just pennies on the dollar.

The concepts set forth by the invention further serve as a model bywhich government medicaid, and medicare programs would save hundreds ofmillions of dollars each year in expenditures. Nationally, the totalsavings in Gross National Product for the United States could exceed 20billion dollars annually if the treatment for dermatophyte infectionsalone were fully implemented.

While providing considerable savings to each nation of the world, mymedication will greatly expand the size of the antifungal drug market.The economically disadvantaged throughout the world, who are currentlyexcluded from this market because of high cost, and weak performance ofthe prior art over the counter topical treatments, will purchase myproduct because of its dramatic effectiveness. New veterinary uses, notcurrently existing, will also contribute to a larger consumer marketthan ever before. Add to this an overseas market, aimed at producing aproduct for developing countries, and the total consumer base for theseproducts will expand by hundreds of millions of individuals, currentlyexcluded from the market by the high cost, and ineffectiveness of priorart treatments.

Now, and finally, an antifungal treatment exists that can save ournation alone, billions of dollars each year in the treatment ofdermatophyte infections alone. A drug that will greatly expand the sizeof the market for antifungal treatments, bring rapid cure to tens ofmillions of suffers in our country, and around the world, and provide animportant weapon in the war against the more serious infectious diseasesthat will save lives as well.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a molecular diagram of phenol.

FIGS. 2-13 show molecular diagrams of compounds of the currentinvention.

FIG. 2 is a molecular diagram of ortho-methoxyphenol.

FIG. 3 is a molecular diagram of vanillyl.

FIG. 4 is a molecular diagram of 3-methoxy-4-hydroxybenzylamine.

FIG. 5 is a molecular diagram of vanillylamide.

FIG. 6 is a molecular diagram of the capsaicinoids.

FIG. 7 is a molecular diagram of piperidine.

FIG. 8 is a molecular diagram of the pungent alkaloid principals ofpepper.

FIG. 9 is a molecular diagram of eugenol

FIG. 10 is a molecular diagram of curcumin.

FIG. 11 is a molecular diagram of gingerol.

FIG. 12 is a molecular diagram of resiniferatoxin.

FIG. 13 is a molecular diagram of tinyatoxin.

FIGS. 14-25 show molecular diagram of common prior art antifungal drugs.

FIG. 14 is a molecular diagram of amphotericin B.

FIG. 15 is a molecular diagram of nystatin.

FIG. 16 is a molecular diagram of griseofulyin.

FIG. 17 is a molecular diagram of tolnaftate.

FIG. 18 is a molecular diagram of ciclopirox.

FIG. 19 is a molecular diagram of imidazole.

FIG. 20 is a molecular diagram of clotrimazole.

FIG. 21 is a molecular diagram of miconazole nitrate.

FIG. 22 is a molecular diagram of econazole nitrate.

FIG. 23 is a molecular diagram of triazole.

FIG. 24 is a molecular diagram of fluconazole.

FIG. 25 is a molecular diagram of terconazole.

BEST MODES FOR CARRYING OUT THE INVENTION

A medicinal preparation of pepper, and its active constituents may beadministered in a wide range of conventional drug vehicles and carriers.Capsicum, and black pepper are available commercially as oleoresin, in awide range of concentrations, and pungencies, and may be used in placeof the plant product described below.

The various preparations described below are made from a moderatepungency commercial grade of ground cayenne pepper (capsicumfrutescens), or black pepper (piper nigrum), as an indicator ofapproximate concentration within each carrier. Their equivalents may beestimated, and prepared from commercially available oleoresin, or fromany of the pungent principals, some of which are also availablecommercially in pure natural, or synthetic form.

The term "pepper", or "pepper compounds" are used somewhat genericallyto indicate a "pungent botanical". Other botanicals such as those of theZingiberacea family including ginger (Zingiber officinale), turmeric(Curcuma longa), cardamon (Elettaria cardamomum), Melegueta pepper(Aframonum melegueta), members of the Euphorbia genus includingEuphorbia resinifera, poinsetta (Euphorbia pulcherrima), clove (Eugeniaaromatica), allspice (Pimenta officinalis) and others having similarconstituents may be prepared in the same way as pepper by following thegeneral procedures outlined below in the capsicum pepper illustrationbelow. Included among this list of botanicals is of course the othermembers of the Solanacea pepper family including members of the capsicumgenus with the annuum, baccatum, and longum species. Among the Piperaceafamily, species of the peperoma, and piper genus which include theretrofractum, nigrum, and longum species. Other species of plants havingsimilar chemistry may also be used in place of the above.

The performance of each preparation will of course depend on type, andconcentration of botanical, carrier, and solvent used in relation to theparticular pathogenic organism involved. The chemical properties, andsolubility of many of these botanical compounds, including informationon separation, and quantitation of their constituents are also availablefrom similar sources in the scientific literature, and and may beconsulted for more detailed investigations.

For purposes of research, or the treatment of disease, the individualcompounds responsible for the pungent quality of red peppers, and othercapsicums may be obtained directly from ground red pepper, according toprocedures described in the article "Separation and Quantitation of RedPepper Major Heat Principals by Reverse Phase High-Pressure LiquidChromatography" by Patrick Hoffman et. al., in the Journal ofAgricultural Food Chemistry 1983, Vol. 31, pages 1326-1330. Thoughseveral related capsaicinoids have been identified in trace amounts, themajor capsaicinoids (FIG. 6) include:

Capsaicin. C₁₈ H₂₇ NO₃

(N-[(4-hydroxy-3-methoxyphenyl)methyl]8-methyl-6-nonenamide).

Dihydrocapsaicin. C₁₈ H₂₉ NO₃

(N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnonanamide).

Norcapsaicin. C₁₇ H₂₅ NO₃

(N-[(4-hydroxy-3-methoxyphenyl)methyl]7-methyl-5-octenamide).

Nordihydrocapsaicin. C₁₇ H₂₇ NO₃

(N-[(4-hydroxy-3-methoxyphenyl)methyl]-7-methyloctanamide.

Homocapsaicin. C₁₉ H₂₉ NO₃

(N-[(4-hydroxy-3-methoxyphenyl)methyl]-9-methyl-7-decenamide).

Homodihydrocapsaicin. C₁₉ H₃₁ NO₃

(N-[(4-hydroxy-3-methoxyphenyl)methyl]-9-methyldecanamide).

N-vanillyl-n-nonamide. C₁₇ H₂₇ NO₃

(N-[(4-hydroxy-3-methoxyphenyl)methyl]-n-nonamide).

Nonanoic acid vanillylamide. C₁₇ H₂₉ NO₃

Decanoic acid vanillylamide. C₁₈ H₃₁ NO₃

Other capsaicinoids, not listed here, are identified in researchliterature as trace elements within capsicum, and may be used inmedicinal preparations as well, along with other analagous compounds.

Capsaicinoids may be generally classified as acid amide derivatives ofphenol (FIG. 1). The characteristic pungent, irritating sensory effectsof these compounds are typical of acid amides, whether derived fromphenol, or piperidine (FIG. 7).

Phenol (FIG. 1), though lacking pungent flavor, is highly corrosive,caustic, and toxic, deriving many of its properties from its basicbenzene structure. While this gives phenol certain antimicrobialproperties, it is generally considered to be unsuitable for therapeuticuse in man, and animals, due to it's high toxicity, and irritatingeffects on tissue.

With the addition of a methoxy goup (OCH₃) to phenol, methoxyphenol isformed. In the ortho position, we have ortho-methoxyphenol (FIG. 2),also known as guaiacol, an extract obtainable from trees of the guaiacumgenus. The effect of this methoxy group in part is an increase inaromacy, and a decrease in toxicity, and caustic properties otherwiseexisting in phenol, yet without apparent decrease in antimicrobialproperties. The attachment of hydrocarbon groups to the ring structure,to form higher analogues apparently increases the antimicrobialproperties of methoxyphenol, and phenol. It is presumed that the meta,or para isomers of methoxyphenol have similar properties to the ortho,in like manner to the similarities between the phenol isomers.

The addition of the methylene group (CH₂) in the para position toortho-methoxyphenol produces vanillyl (FIG. 3). Like phenol, andmethoxyphenol, it is presumed that changing the position of themethylene group to form other vanillyl isomers will produce compounds ofsimilar, although not exact properties to that of vanillyl.

The vanillyl structure on which the capsaicinoids are constructed isalso typical of the pungent principals found in ginger (zingiberacea)species of plants.

Collectively known as gingerol (FIG. 11): shogaol, paradol, zingerone,gingerol and other analogs, have a different side chain than thecapsaicinoids, and lacking an ammonia (NH_(n)) group, are neitheramines, or amides like the capsaicinoids or piperidines. Hydrolysis ofgingerols yield vanillyl, and a fatty acid side chain, both of whichdemonstrate like therapeutic properties to the capsaicinoid hydrolytes.

Also members of the ginger, or Zingiberacea family, turmeric (Curcumalonga L.) contains the compound curcumin (FIG. 10), actually a vanillalderivative differing from vanillyl by one hydrogen (H) atom having an(CH) substituent, rather than a methylene (CH₂) in the para position.This analog differs further with a side chain unique from the others.Cardamon, allspice, clove, black pepper, and many others containeugenol, another vanillyl analog with yet another hydrocarbon sidechain.

Other botanical sources of vanillyl analogs include gum euphorbium, andextract of certain species of the Euphorbia genus, which contain thecapsaicin analog resiniferatoxin (FIG. 12), along with its analogtinyatoxin (FIG. 13) and others.

Replacement of one of the hydrogen (H) atoms of ammonia (NH₃), withvanillyl, and the replacement of the other hydrogen (H) atom with anorganic hydrocarbon group produces vanillylamide (FIG. 5). In the caseof the capsaicinoids (FIG. 6), or capsaicin analogs for example, thisorganic hydrocarbon group is a chain acid (R'), varying from about 8, to14 carbon atoms, depending upon the particular capsaicinoid. These sidechains, both saturated, and unsaturated (including add to the pungencyof capsicums, and themselves possess antimicrobial properties of theirown, without apparently contributing corrosiveness, or toxicity tovanillylamide.

Hydrolysis of capsaicinoids yield active agents as well. The splittingoff of the side acid chain, and it's replacement with a hydrogen (H)atom yields the primary amine vanillylamine, or3-methoxy-4-hydroxybenzylamine (FIG. 4) from vanillylamide (FIG. 5), inthe case of all capsaicinoids. Conversely, the side acid chain,receiving a hydroxy (OH) group, is converted to a fatty acid, and yieldsa different hydrolyte for each individual capsaicinoid. In the case ofcapsaicin (FIG. 6), hydrolysis of the side acid chain R' (FIG. 6)CO--(CH₂)₄ --CH═CH--(CH₃)2 yields iso-decylenic acid COOH--(CH₂)₄--CH═CH--CH--(CH₃)₂.

The piperidines (FIGS. 7 & 8)), represent a group of analogous alkaloidcompounds from which most of the pungent principals found within plantsof the piperacea family, of which black pepper (piper nigrum) is amember, are found. Also classified as acid amides, the piperidines, likethe capsaicinoids found in capsicum species, are primarily responsiblefor the characteristic sharp, pungent taste of black pepper.

The piperidine ring (FIG. 7) structure is diverse from that of phenol(FIG. 1). Though also a six membered, carbocyclic compound, piperidinesinstead contain one nitrogen (N) hetero atom within the ring. Piperidineis heteroparaffinic, and contains no double bonds. The hetero nitrogenatom within the ring is a contributor to the pungency of thesecompounds. The attachment of a hydrogen (H) atom to the hetero nitrogenatom within the ring forms the amine structure. Attachment of ahydrocarbon group, in the form of a side acid chain (R" FIG. 8) attachedto a benzene structure establishes the acid amide structure. Thesecompounds include; piperine C₁₇ H₁₉ NO₃ (FIG. 8), chavicine C₁₇ H₁₉ NO₃,piperettine C₁₉ H₂₁ O₃ N, piperidine (CH₂)₅ NH, piperyline, piperoleinA, piperolein B, piperanine, and others.

Hydrolysis of piperidines, like the capsaicinoids, yield active, pungentcompounds. Chavicine, for example is hydrolysed to piperidine, whichreceives an additional hydrogen (H) atom to form a primary amine, andchavicic acid, which receives the hydroxy (OH) group to form the fattyacid.

Hydrolysis of these capsaicinoid, and piperidine acid amides, as well asthe other listed compounds may be accomplished with chemical catalysts,or by boiling a liquid preparation of these compounds with water.Hydrolysis does not appear to diminish the pungency of these compounds,and in some cases actually appears to enhance both their pungency, andtherapeutic action.

The carbonyl group (C═O) side chain substituent, common to all the abovecompounds (except eugenol) is also believed to be a contributor toantimicrobial activity.

The chemical structure of prior art antifungals (FIGS. 14-25) useneither the phenolic, or piperidine (FIGS. 7 & 8) amine, or amidestructures. The current trend appearing to favor azole derivatives.These include the imidazole (FIG. 19) derivatives such as clotrimazole(FIG. 20), miconazole (FIG. 21), ketoconazole, econazole (FIG. 22), andothers. The newer triazole (FIG. 23) class includes fluconazole (FIG.24), terconazole (FIG. 25), itraconazole, and others.

Other active agents found within capsicum include citric acid, vitaminsA, B₁, B₂, C, and E, iron, potassium and niacin in significantquantities, along with other lipids, and carotenoids includingcapsanthin, capsorubin, and others. Vitamin C concentrations of 100milligrams per ounce, are the highest of any natural food compound.Vitamin A content is also high, with 6170 I.U. per ounce.

An infusion of pepper may be prepared by soaking approximately 4 cm³(1/4 teaspoon) of commercially available ground red, or black pepper, toone liter (1 quart) of water of sensibly comfortable temperature.Infusion should be allowed to soak at least ten minutes before use forbest results. According to preference, infusion may, or may not bestrained to remove plant residue before use.

A tea of is a more potent version of infusion above, using about 16 cm³(1 teaspoon) of ground pepper for each liter (quart) of sensiblycomfortable water. Tea may also be prepared from boiling water, oritself be boiled in water before use. Boiling pepper in water assurescomplete hydrolysis of the pungent principals, which are also activeagents.

A tincture may be prepared by soaking ground red, or black pepper in asolution containing approximately 60% ethanol, and 40% water. Pureethanol, and other solvents such as acetone, chloroform, vinegar (aceticacid), and others may also be used. The fluid volume of the solution maybe about three, or four times that of the dry volume of the groundpepper. The mixture should be agitated, at least occassionally, over aperiod of at least two hours, with maximum extraction being obtainedafter about six hours. Allowing the mixture to sit over night producesexcellent results. Before use, the residual ground pepper may bestrained off, and liquid tincture saved for use.

A preparation of pepper drops may be obtained by reducing tincturethrough heat, or passive evaporation. Drops made by this method aresimilar in purity to some grades of commercially available oleoresin ofcapsicum, and black pepper.

A plaster, or poultice may be prepared by mixing ground pepper withwater, until it has a paste-like consistency that will assure goodadherence to the skin, or cloth to which it is applied.

A lotion, cream, or shampoo may be obtained by adding to anycommercially available shampoo, cream, or lotion, a portion of drops, ortincture equal to approximately 25% of the volume of lotion, cream, orshampoo carrier.

A douche is prepared from infusion, or tea that is strained of the plantresidue material before use.

A suppository is made from drops in cocoa butter, or gelatin in the samestrength as douche, or lotion.

An injection is prepared from a purified version of infusion, tea,drops, etc., administered intravenously, in tissue, or mixed with, andinjected into the spinal fluid.

A powder is pepper in ground form, or extracts mixed, and/or boundwithin a binding powder carrier such as talc.

Pepper, and any of its active constituents may be administered as ageneral antiinfective in the treatment of disorders including fungal,and bacterial infections.

Pepper extracts may be administered within conventional drug vehicles,and carriers, and are recommended for use in four basic concentrations.Recommendations for treatment given below are general, and may bealtered to suit specific conditions. If one recommended concentrationfor some reason appears unsuitable, the next graduation should be used.

Other botanicals such as ginger, turmeric, cardamon, clove, poinsetta,ect. which have many therapeutic properties in common with pepper, maybe used in place of pepper described below. Though these botanicalsshare common properties with pepper, variable results between the twoare to be expected according to concentration of botanical product, thecarrier, and solvent used, and the particular pathogenic organisminvolved. With this in mind, modifications to the recommendations givenbelow are sometimes warranted depending on specific circumstances. Ifone recommended concentration is not suitable, a different one may betried. Factors to consider are the degree of tissue damage, patientsensitivity to the medication, and certainly how anxious the patient isto be rid of the disorder! In most, if not all cases, daily treatmentneed not be continued beyond the first few weeks to completely resolvedermatophyte infections.

In the lower concentrations, an infusion may be used in the treatment ofmilder microbial infections including dermatophyte infections,particularly when tissue damage is minimal. Infusion works well as ascalp rinse, a bath for the feet, and skin, and as a douche in thetreatment of candida, and other vaginal disorders. Infusion is alsorecommended if patient sensitivity to the higher concentrations becomessignificant.

In higher concentrations, a tincture, a powder, a poultice, and apreparation of drops, are recommended in the treatment of severedermatophytosis. High concentrates, such as these, are preferred wheretissue damage is significant, and where infection sites are causingconsiderable discomfort for the patient. Drops, for example, work wellfor topical treatment of nail infections, ringworm lesions, and infectedhair. These high concentrates generally produce cure after the firstdose when treating skin lesions, and have a prophylactic action ofgreatest duration, lasting up to about five days after application. Asit is usually necessary to induce substantial healing of the skin as ameasure against recontamination, and reinfection of dermatophytes, thehigher concentrates appear to be most effective as prophylactics aswell.

A tea represents a moderate concentration of pepper compounds. It may beused in the same manner as infusion, or in the treatment of more severecases of dermatophytosis. Tea should be used if infusion fails to bringimmediate relief of secondary symptoms, such as itching in athlete'sfoot, candida, or jock itch, within one hour of the first treatment.

Tea may also be used in place of the higher concentration carriers, suchas drops or tincture. It is often equally effective in curing severecases of dermatophytosis, in which there is significant tissue damage,as the high concentrates. In this case, tea is preferred over the highconcentrates, particularly if the patient sensitivity to the medicationis causing significant discomfort.

Tea is also suitable as a gargle, or mouth rinse for thrush, or otherfungal infections of the throat, and oral cavity.

For an injection of pepper compounds in deep tissue, spinal fluid, orintravenously, milder concentrations, such as infusion are recommendedfor initial treatment. While injection of pepper extracts such ascapsaicin have been administered safely in animal testing of analgesics,it is not known at this writing if data exists on treating humans withinjection of pepper compounds.

A lotion, or shampoo may be prepared with any commonly available lotion,or shampoo, and applied to infected areas in its intended manner. Othertherapeutic agents, in addition to pepper extracts, may be added toshampoo and lotion. If irritation is a concern, a topical anesthetic,such as lidocaine, or benzocaine may be added to lotion to reduceseverity. If skin is very dry, emollients may also be added to lotion.

A pepper aerosol may be inhaled in the treatment of throat, andrespiratory infections. In this administration, aerosol should bederived from a lower concentration such as infusion, as pepper isextremely irritating to the nose, throat, lungs, and eyes, especiallywhen airborne. This is especially true of capsicum aerosol. For thisreason, aerosol is somewhat limited in it's medicinal application.

The irritating effects of pepper aerosol, and particularly capsaicum, isgreater when distributed within an etheric tincture solution, such asalcohol, ether, chloroform, or acetone. Once airborne, even minuteconcentrations have a tear gas, or macelike effect on the eyes, andrespiratory system. A single, half second spray of a cayenne pepperethanol tincture (60% ethanol/40% water works well) aerosol from a handheld dispenser is sufficient to render a fifteen hundred square footenclosed area uninhabitable to humans, and animals, as choking,coughing, and burning irritation to the eyes and respiratory system makehabitation of the room intolerable.

While this may limit the use of aerosol for medicinal applications, itappears to have tremendous potential for military, and paramilitaryapplications, particularly as a safe and more effective alternative totear gas, and other antipersonnel aerosols. Pepper aerosol also showgreat potential in agriculture as a crop antiinfective/antifungal,insecticide, and pest repellent.

Pepper powder is also very irritating when airborne, and like aerosol,has a more limited medical application than the other carriers. If usedas a foot powder for example, it is best to fix the pepper compoundswithin a powder binder such as talc, to prevent, or lessen escape ofairborn particulate.

As to the therapeutic properties of pepper compounds, and are severalactions I believe to be at work in the operation of the medication ofthe current invention. While some of the actions described below arefactual, others are theoretical, or hypothetical, and are set forth aspossibilities, and are not intended to be binding. They represent anattempt to further explain the operation of the current invention, andto give direction to areas warranting further research.

The first therapeutic action of pepper extracts upon administration isthat of an irritant, or as I prefer to call an inflamatory. The irritantconstituents of capsicum, namely the capsaicinoids (FIG. 6), theirhydrolytes, and the other acid amide piperidines (FIGS. 7 & 8), andtheir hydrolytes found in black pepper, and related compounds are allinstrumental in precipitating a rapid inflamatory response in the areaof administration. This is observed, for example, when applied to skinin the treatment of various forms of tinea. The area of treatment oftenturns red, or pink, and feels warm or hot. Burning, or warm tingling issometimes reported by patients after topical administration of pepperextracts, usually the result of excessive dosage, or exposure to opencuts in tissue. Though this burning sensation can become quite intense,it does not usually last beyond the first five or ten minutes aftertreatment. The burning subsides into a warm, tingling sensation that isno longer uncomfortable to patients. The induction of inflammation tothe point of pain is accidental, and not necessary for cure.Inflammatory responses associated with even slight warmth and rednessare more than adequate to provide sufficient therapeutic action.

The therapeutic value of inflammation, is the stimulation of the body'sown immune response in the area of infection. This precipitates a variedarray of fungistatic serums, including leukocytes, and other mononuclearcells in the area of infection. These fungistatic serums inhibit thegrowth of pathogenic fungi.

Inflamation also increases the rate of skin shedding, which combatspenetration of the fungus, or other organism into the skin. In this modeof action, the microbe is essentially "cast off" with the diseasedtissue. Perhaps or this reason, those varieties of dermatophytosis thatare accompanied by inflammation often eventually heal on their own. Thenoninflammatory varieties such as dry athlete's foot, however becomechronic, and are very difficult to heal. The lack of participation ofthe immune responses of the host prevents healing, and cure.

Pepper compounds are believed to act as an adjuvant to these fungistaticserums, by facilitating their pathways through the blood vessels, andskin of the host, and through the cell wall of the fungi, or otherpathogen. Being composed primarily of lipids, capsicum for example isbelieved to increase the permeability of the cellular membrane of boththe host, and fungi. In addition to aiding the delivery of antifungalserum, the increase in cell membrane permeability also facilitates thedelivery of undecylenic acid, another antifungal compound found insweat, into the fungi. With the aid of increased permeability providedby pepper compounds, these antifungal compounds, which are normallyfungistatic, become fungicidal.

The direct antimicrobial properties of pepper and another of the notablypungent botanicals ginger may be observed in vitro, in addition to thoseobserved in vivo in the actual treatment of disease.

A series of in vitro tests are conducted on 3 tincture samples preparedfrom the ground spice of cayenne pepper (Sample A), black pepper (SampleB), and ginger (Sample C). Each spice is measured, and mixed with pureethanol in an amount three times the measured volume. The mixtures arestored for 18 hours at room temperature (22° C.), and agitated on 5separate occassions over the period. The mixtures are then strained ofresidue, and submitted for testing. Also included is Sample F; atincture prepared with commercially pure capsaicin(8-methyl-N-vanillyl-6-nonenamide) at a concentration of 25 mg./ml. pureethanol.

Initial in vitro tests performed by a medical university laboratoryreport that none of the Samples A, B, C, or F show antimicrobialactivity against Candida albicans, or Neurospora crassia on a solidmedium, carrot juice agar (pH 6) screening. A liquid assay in vitroscreen performed by a major U.S. pharmaceutical company however, revealsactivity against all 11 strains of pathogenic fungi tested, including 7strains of Candida! These pathogenic strains are responsible for deeptissue mycotic infection, although the Candida strains also causesuperficial mycotic infections of the skin, and mucosa as well.

At first glance, a general hierarchy of activity relative to the degreeof pungency among the botanical Samples A, B, & C is evident, withcayenne pepper being most pungent, followed by black pepper, and thenginger. Though exceptions are evident in the tests, degree of pungencyis an accurate general "rule of thumb" with regard to evaluating therelative effectiveness of the botanicals. This observation however, forreasons set forth below, should not be interpreted as an indication thatthe therapeutic effects of the botanicals are determined solely by thedegree, and quantity of pungent principals present in the Samples,though it is a factor. This will be further addressed below.

Perhaps most intriguing of the test results below is that Samples A, B,C, & F of the current invention show greatest activity against thosefungal strains most resistant to the drug standard Amphotericin B! Inparticular, C. albicans ATCC 38247, C. kefyr ATCC 28838, and T. glabrataATCC 15545 show particular sensitivity to Samples A, B, C, & F in thisscreen. These strains, being most resistant to standard drug therapies,pose the greatest potential for causing life threatening illnesses. Thenecessity of prolonged treatment with high dosages of highly toxicantifungal drugs required to treat these diseases is often itself lifethreatening to the patient.

Another important feature of these test findings is evidence of thepresence of multiple antimicrobial compounds within the Samples. Incomparing Samples A & F for example, it is apparent that theantimicrobial action of cayenne pepper (Sample A) cannot be whollyattributed to the presence of capsaicin alone in the ground spice.

A review of the aforementioned article "Separation and Quantitation ofRed Pepper Major Heat Principals by Reverse Phase High Pressure LiquidChromatograph" indicates by rigorous testing a total "capsaicinoid"content not exceeding about 1.9 mg./gram in common red pepper. Sample Abeing diluted 3 times with ethanol would fix its maximum capsaicinoidcontent at perhaps 0.063%, or about 630 ug./ml. Capsaicin accounting forabout half of the total capsaicinoid content of common red pepper, wouldfix the capsaicin content of Sample A at about 0.032%, or about 320ug/ml. This diluted 256 times shows Sample A as having activity againstC. albicans ATCC 38247 at a capsaicin concentration of less than 1.25ug./ml., and total capsaicinoid content of less than 2.5 ug./ml againstwhich Amphotericin B requires a concentration of 25 ug/ml.!Additionally, capsaicin though the most toxic compound found in anysignificant amount in capsicum peppers, is much less toxic thanAmphotericin B!

In comparison, Sample F has a concentration of pure capsaicin at 25mg./ml.-about 40 times the total capsaicinoid content of Sample A, yetis still short of the Sample A performance accross the board! This canonly mean the presence of another antifungal compound, and/or asynergistic relationship between the mix of capsaicinoids and othercompounds within the botanical that account for the total antimicrobialeffect. It may also suggest that the therapeutic actions of thesebotanicals are not generally improved by extensive isolation of theirindividual constituents, and that the total therapeutic mechanismsinvolved are quite complex, involving a substantial number of compoundsin addition to the phenols, and piperidines present. In this respect,high purification of individual constituents has the undesireable effectof to some degree dismantling the full therapeutic action of thecompound.

Sample F is the exception containing a purified isolate (capsaicin) ofthe primary pungent principal found in red pepper and other capsicums.Sample F also has perhaps 3 times the capsaicinoid, and 6 times thecapsaicin content of the most pungent species of capsicum known to existin nature. Yet accross the board, Sample F falls short of the basicbotanical extract Sample A even though it has 40 times the capsaicinoidconcentration of Sample A!

While the above tests provide important insight into some of thetherapeutic actions of the current invention, they are of course onlypartially indicative of the full antimicrobial action present, even asthe earlier carrot juice agar tests failed to reveal any activity atall. The fuller antimicrobial activity of the compounds described aboveare of course observed in vivo in the actual treatment of disease,wherein the bodily immune responses are also modulated. These compoundsrepeatidly cure dermatophyte infections in as few as a singleapplication. Can this be said of Amphotericin B, or any of the othercurrently available topical treatments? Absolutely not!

    ______________________________________                                                     Minimum Inhibitory Concentration                                                test sample    standard                                          (number of dilutions) μg/ml                                              Organism       A      B     C    F    Amphoter.B                              ______________________________________                                        Candida Albicans                                                                             16     16    8    8    1.56                                      ATCC 10231                                                                    Candida Albicans 16 16 8 8 1.56                                               579a                                                                          Candida Albicans 16 16 16 16 1.56                                             442                                                                           Candida Albicans 256 16 8 256 25.00                                           ATCC 38247                                                                    Candida Albicans 16 16 8 8 1.56                                               ATCC 62376                                                                    Candida tropicalis 16 32 16 16 1.56                                           NRRL-Y-112                                                                    Candida kefyr 64 32 16 16 3.12                                                ATCC 28838                                                                    Torulopsis glabrata 16 32 16 8 3.12                                           ATCC 15545                                                                    Cryptococcus albidus 4 8 8 16 1.56                                            ATCC 34140                                                                    Saccharomyces cerevisiae 16 16 8 16 1.56                                      GSI-36                                                                        Aspergillus niger 16 4 4 4 1.56                                               ATCC 16404                                                                  ______________________________________                                         Spec: Yeast extract Nitrate Broth + Glucose, water solvent, 48 hour           Incubation, all Samples precipitate at 50% in YNB + G.                        Sample A = cayenne pepper*                                                    Sample B = black pepper*                                                      Sample C = ginger*                                                            Sample F = capsaicin                                                          (commercially pure 8methyl-N-vanillyl-6-nonenamide) 25 mg/ml pure ethanol     *tinture 3:1 ground spice and ethanol 18 hours @ 22° C.           

The irritant acid amides found within both kinds of pepper, and theirhydrolytes, appear to have direct fungicidal actions. Isodecylenic acid,one of the hydrolytes of capsaicin, is believed to have antifungalproperties superior to it's fatty acid chain relative, undecylenic acid,and offers important clues to the developement of still otherantimicrobials, structured similarily for increased effectiveness.Another hydrolyte of the capsaicinoids, 3-methoxy-4-hydroxybenzylamine(FIG. 4), suggests a new class of amine antimicrobial compounds, derivedfrom this, and other analogus structures.

Other possible antimicrobial agents found in pepper plants, that mayplay a role in producing curative results, are known as phytoalexins.Phytoalexins, such as the compound capsidiol, found in plants of thesolanacea family which includes capsicums, are a group of antimcrobialagents, not normally present in the plant, that are produced by theplant, only in response to trama caused by heat, cold, mechanicalinjury, or attack by insects, or microbes. Capsidiol, and other of thephytoalexins produced by solanacea species, are known to have antifungalproperties against fungi that are pathogenic to solanacea species ofplants. While these fungi are not patogenic to man, it is possible thatcapsidiol, or another phytoalexin produced in response to theirchallenge, has antifungal action against fungi that are pathogenic toman, as well as those pathogenic to plants. It is therefore possiblethat capsidiol, or another phytoalexin may play a role in curing fungaldisorders in man and animals, as well as plants.

Dehydration is another possible therapeutic action of pepper compounds.In the treatment of superficial mycoses, pepper extracts appear to drythe skin to a degree that may be inhospitable to fungi. Perhaps theresult of increased permeability, or the formation of salts on the skin,the skin, though drier, is not uncomfortably so, and may have at least afungistatic effect as a result of reduced hydration.

The prophylactic action of pepper extracts is another importanttherapeutic feature of the current invention. In addition to havingimmediate fungicidal action in the treatment of superficial mycoses,pepper compounds remain in the skin for perhaps ten days aftertreatment, to prevent reinfection. Patients often report thereoccurrence of the warm, tingling sensation in treated areas whilebathing, days after treatment. Exposure to water appears to alsorestimulate its therapeutic action as well. If feet, or skin becomemoist, and sweaty, the therapeutic action is intensified, at the samepathogenic fungi would otherwise proliferate. This provides a shieldagainst reinfection due to recontamination, and protects the skin whileit heals.

Pepper compounds also function as a vulnerary, aiding, and acceleratingthe healing and regeneration of tissue. As tissue damage can be severein certain forms of dermatophytosis, such as favus, nail infections, andathlete's foot, it becomes necessary to heal the damaged tissue beforefull cure is possible. Pathogenic fungi, finding opportunity in damagedskin for example, will often continue to reinfect those areas unless theskin is healed. This is one reason prior art medications are soineffective towards cure. It becomes necessary to heal the skin tosafeguard against repeat infection, as healthy, whole skin is the bestprotection against reinfection. As capsicum for example, is particularlyhigh in vitamins, and other nutrients, they also appear to have ahealing effect on damaged tissue.

The power of pepper compounds to excellerate healing of injured tissueis also quite dramatically demonstrated in the treatment of lacerations.We commonly have treated the most stubborn, long lasting lacerationinfections with pepper compounds (lotion containing hydrolysed blackpepper drops is a personal favorite), only to witness within just hours,reductions in redness, swelling, sensitivity, and exudate that are quitefrankly hard to believe! One is equally astounding upon witnessing theimprovement seen in just a day or two after treatment!

A medication such as described above is an invaluable wound healingtreatment, particularly for the immune suppressed, and should be used totreat cancers, and other neoplasms.

Pepper compounds are also unbelieveably effective in the treatment ofburns, and abrasions. On several occassions I have treated burns withpepper lotion with results as astounding as with lacerations. Theimprovement in the healing of the skin is quite notable within hours,with continued improvement in the following days that is nothing shortof astounding. This also is very important to burn patients, and islikely to excellerate recovery to a degree that will save the lives ofmany that would otherwise die from their injuries.

Pepper compounds could be injected into deep tissue to excellerate thehealing of buises and contusions. This would be of great benefit toathletes, and accident victims.

Other antimicrobial actions of pepper compounds are perhaps due to thehigh concentration of antioxidant compounds such as vitamin E, aromaticamines, phenols, and amino phenols found in pepper, particularlycapsicum. These antioxidants may interfere with the action of digestiveenzymes secreted by the fungi, that are necessary for ingestion ofnutrition, in effect starving the fungi. It is also possible that highconcentrations of citric acid, or vitimins found in pepper, are directlytoxic to the fungi.

Conversely, the very high concentration of vitamin C, a known oxidant,may also interfer with the ability of the fungi to digest, and ingestnutrition, by instead oxidizing it's food compounds before they can beabsorbed, also depriving the fungi of food.

Since capsicum is so high in vitamin A, the B complex, C, D, and E, itcan be used to treat several nutritional disorders including scurvy,pellagra, beriberi, rickets, xerophthalmia, and a host of relateddiseases. Significant amounts of iron, and potassium, make it excellentfor correcting fluid absorption, and retention imbalances that resultfrom dehydration due to diarrhea, and vomiting. Infusion, or tea ofcapsicum may be given to correct dehydration due to diarrhea. Soakingthe ground powder only briefly in cool water, to produce a cold tea, orinfusion should be sufficient to release the water soluble C, and Bvitamins, and mineral salts, without releasing as many of the pungentprincipals, which may make ingestion difficult.

Other evidence of the healing, and regenerative properties of pepper isobserved in the treatment of other skin diseases such as psoriasis,dandruff, seborrhea, and other forms of eczema. Topical treatment ofthese disorders with pepper, within the same drug vehicles and carriersdescribed here in the treatment of fungal disorders, produces curativeresults that are equally astounding. As these diseases are not believedto be of microbial origin, they are none the less completely healed,usually without relapse, after as few as one single treatment! This isfurther evident that pepper compounds stimulate the healing process ofthe skin, and encourage regeneration, growth, and normalization oftissue function.

Pepper compounds also appear to possess keratolytic actions, which aidhealing of these general forms of dermatitis, by aiding in the breakdownof keratin in the skin. This also makes them useful in the treatment ofwarts, corns, callouses, acne, wrinkles, and cancers. Keratolytic actionmay also have an antimicrobial effect, by perhaps interfering with theability of pathogenic microorganisms such as fungi to digest, or ingestthe keratin on which they feed.

In one study, a four year old girl, with chronic seborrhea of the scalp,was completely healed of the disorder after just three treatments withcapsicum drops. The girl has two lesions, approximately 25 mm (1")diameter on the top portion of her scalp, that she has had sinceinfancy. The lesions are tightly packed with thick, yellowish whitescales approximately 2 mm (1/16") in diameter. The area above thelesions is covered with loose scales, that are seen whenever the hair isparted.

The two seborrhea lesions are treated topically, with capsicum drops,prepared from heat evaporated tincture. The dosage is once a day forthree consecutive days.

Within the first few weeks, the lesions gradually lose their superficialloose scales, leaving only the tightly packed scales that are the lesionitself. At three weeks, however, even the tightly packed scales havedisappeared, and no lesions can be found; the patient is completelyhealed! The area of scalp previously infected with seborrhea is nowhealthy, and normal, and completely indistinguishable from the rest ofthe scalp, which is healthy. It is not possible to determine if the girlhad ever even had seborrhea, as no evidence of the prior disease can befound on very close examination. Subsequent examinations over a periodof several months indicate a healthy scalp, with no recurrence ofseborrhea or any other dermatologic disorder.

Another illustration of the keratolytic properties of pepper compoundsinvolves a 12 year old boy, afflicted with a large plantar wart on theheel of his foot, in which the boy is completely healed after a singletreatment with a pepper extract.

The boy has a large, brownish colored plantar wart on the upper insideportion of the heel of his right foot. For more than two years, the warthas caused the boy mild, to extreme discomfort, particularly whenwalking. On numerous occassions over the course of this period, the warthas been treated with several over the counter, and physician prescribedtopical medications that yield no noticable improvement in thecondition. The boy is accustomed to shaving the wart off at the skinsurface at regular intervals to reduce the size, and hence the degree ofdiscomfort associated with its rapid growth. When the upper layers ofthe wart are removed in this manner, the remainder of the tumor appearsas a cluster of milky-white stones buried below the translucent layersof skin on the heel. Regardless of these continued treatments, the wartcontinues to grow back causing the usual discomfort.

Prior to treatment with pepper drops, the wart is examined, and appearsto occupy a brownish, rough area of the heal approximately 25 mm. (1")in diameter at the base. The central portion is raised, forming a noduleapproximately 6 mm. (1/4") above the skin surface.

The wart is treated topically with one (1) drop of pepper drops thatwere prepared from a standard 4:1 red pepper acetone tincture that wasreduced 40 times by room temperature evaporation. Upon application, theboy reports no notable sensation from the treatment.

Eight weeks after this single treatment, the boy's heel is againexamined, and to the astonishment of the boy and his mother the wart iscompletely disappeared! Close examination of the entire foot shows noevidence of warts. The previously infected area of skin looks perfectlynormal and healed, with no trace of disease, or abnormality.

When asked about details of the course of healing of the wart, the boyreplied that after treatment with the pepper drops, he had experiencedno further discomfort in the area of the wart. This lack of discomfortcaused him to forget about the wart, and he had not looked at it sincetreatment.

The above illustration in addition to demonstrating the keratolyticactivity of pepper compounds also suggest the possibility ofantimicrobial activity. Viruses being a known cause of warts areprobably inhibited by pepper compounds. This in combination with thekeratolytic, and perhaps vulnerary action of pepper are responsible forsuch dramatic healing results. It has been many months at this writingsince the boy's treatment. The wart has not returned, nor have new onesarisen.

From these examples, we see the multiple therapeutic actions of pepper,its constituents, and related compounds for stimulating healing, andregeneration of tissue damaged by both disease, and injury, in additionto its antiinfective uses, and how pepper appears to interact with thebody's own regenerative capabilities to normalize health, and functionof tissue. Many other examples exist which illustrate these sametherapeutic actions at work in the treatment of diseases that causeabnormal growth, and proliferation of keratin including eczema, generaldermatitis, and practically all other dermatologic disorders.

Industrial Applicability

Thus the reader will see, that the current invention provides anantimicrobial treatment, with a degree of effectiveness in the treatmentof fungal diseases that is many generations ahead of the prior art.

Naturally occuring compounds, found in pepper plant species of thesolanacea family, which include the capsicums C. frutescens, C. annuum,C. Baccatum, and the piperacea family which includes the peperoma, andpiper genera, and the well known retrofractum, nigrum, and longumspecies among others, and related compounds, are found to have profoundtherapeutic actions in the treatment of fungal disorders. Thesecompounds may be administered in most commonly used drug deliveryvehicles, and carriers, with outstanding results.

A single topical treatment with my medication is all that is usuallynecessary to provide complete cure for most superficial mycosesincluding ringworm, inflamatory athlete's foot, jock itch and candida.The onset of effect is immediate, with cessation of symptoms usuallywithin the first hour of treatment, and complete healing within thefirst few days.

Prior art topical medications, on the other hand, usually require scoresof applications before full results are seen, and often do not provideadequate cure, much less relief of symptoms even with long term use.

Even recalcitrant cases of dry athlete's foot, which often requiremonths of treatment with prior art systemics, is completely healedusually within less than a dozen topical treatments with my medicine.Severe cases of dermatophytosis such as this, and others, may now betreated topically by the sufferer, with a relative few applications ofan over the counter treatment containing pepper extracts.

Prior art systemic treatments, which require the attendance of adermatologist, and daily multiple doses of the medication over a periodof several months, can cost hundreds of dollars to treat, and are oftenunsuccessful in providing complete cure. In addition to thisconsiderable cost in time, money, and inconvenience, prior art systemicantifungals have many adverse effects, which are not only unpleasant,but can themselves cause serious health problems. The risk of damage tointernal organs, blood composition and adverse interactions with othermedications, are factors that must be carefully weighed by physiciansadministering prior art systemic antifungals. With this, other lesssever, yet unpleasant side effects include nausea, vomiting, headache,dizziness, fever, diarrhea, and many other disorders that contribute tothe misery and ill health of the patient.

With pepper compounds, systemic treatment with prior art antifungals,with their high cost, weak therapeutic action, and adverse side effectsare no longer necessary to treat superficial mycoses. Instead of monthsof systemic therapy that is very costly, time consuming, slow to provideresults, and an endangerment to health, the sufferer can cure thecondition themselves, with a safe, inexpensive, and astonishinglypowerful medicine such as mine.

Pepper compounds are safe, being a food, consumed by man for thousandsof years, and do not induce illness in the patient as prior artantifungals often do. Pepper is widespread throughout the world, and isgrown in virtually every country. Its active constituents, most of whichare pungent acid amide compounds, easily obtainable from the groundproduct, have all been synthesized, and many are available fromcommercial drug and chemical manufacturers.

The amazing healing power of my medicine, coupled with the tremendouseconomic advantage it provides, paves the way for the creation of manynew and very large markets for topical treatment of dermatophytosis.Rather than exclude the economically disadvantaged from treatment, asprior art antifungal do because of their high cost, and meagereffectiveness, my treatment can be produced, and sold for less thanprior art topicals, and still provide a larger profit margin formarketers than is common within that industry. My product will greatlyexpand the market base for tinea medicines alone by tens of millions ofindividuals worldwide, and most importantly, provide effective medicalcare for those most in need of it.

Even severe cases of dermatophytosis, which cost hundreds of dollars totreat with prior art antifungals, can be completely cured in less time,and for less than one cent worth of pepper. A product such as this, soldfor just one dollar, will attract many millions of consumers to themarket, who are currently excluded because of the high cost andineffectiveness of currently available prior art topical antifungals.

The high effectiveness, low toxicity, and very low cost of My medicationwill greatly broaden the size of the veterinary market for treatment ofmycoses. The high effectiveness, low toxicity, and very low cost of mymedicine also makes feasible the creation of a significant market fortreatment of mycoses within the livestock industry. Being highlycontagious, and finding opportunity under certain common weatherconditions, dermatophytoses such as ringworm for example, can becomeepidemic within a herd, within a very short time, disqualifying themfrom sale at the feed lots.

The weak therapeutic action, and high cost of prior art topicalantifungals has prevented the formation of a market for the treatment oflivestock for superficial mycoses. To treat food animals such as cattle,with any of the prior art topical antifungals before market is an absurdnotion. The cost of medicine, its very slow action, coupled with thevery considerable amount of labor required to repeatedly administer themedicine, can never be justified from an economic standpoint. For thisreason, no significant market exists within the livestock industry forsuch products.

With the treatment of the current invention, however, the combination ofsafety, low cost, and astonishing effectiveness, make it noweconomically feasible to establish a product for treatment of ringworm,candida, and other superficial mycoses within the livestock industry, aswell as for deep tissue microbial infections. Being derived from foodcompounds generally recognized as safe (GRAS) by the U.S. Food and DrugAdministration, my medication is especially appropriate for use in thelivestock industry. With my medication, an outbreak of ringworm within aherd, in the last week before market, need no longer prevent them frommarket as before. In addition to topical application, analogs ofpepper's active agents may be added to livestock feed to preventsystemic diseases as well.

Pepper, and it's active constituents provide an important research toolin the treatment of deep tissue fungal disorders, as well as thesuperficial varieties. The almost universal interchangeability ofantifungal medications, between topical and systemic adminsitration,suggests the use of pepper compounds for systemic, as well as topicaluse in the treatment of deep tissue mycoses. Pepper extracts may begiven by injection into the blood, spinal fluid, or directly intodiseased tissue for the treatment of aspergillosis, actinomycosis,crytococcocis, entomophthoromycosis, histoplasmosis, blastomycosis,coccidioidomycoses, paracoccidioidomycoses, candidiaisis, and other deeptissue fungal disorders. Analogs of pepper's active constituent may alsobe developed for oral administration to prevent decomposition as aresult of digestive processes.

With the very rapid increase in the incidence of deep tissue fungaldisorders, and projections suggesting even greater incidence in thefuture, the need for safer, more powerful treatments is more crucialthan ever. Finding opportunity in immunocomprimised patients such asorgan transplant patients, and others on immunosuppressant drugs, andthose suffering from AIDS; these diseases are life threatening.

Also life threatening to immunocomprimised patients, is treatment withprior art antifungals. Their high toxicity, and multiple adverse sideeffects often have devastating impact on the health of these patients,who are already very sick. Complications from these adverse effects canwell end their lives, in addition to adding extra misery to theiralready tragic circumstances. The risk of damage to internal organs,changes in blood composition, and adverse interactions with othermedications, along with the nausea, vomiting, diarrhea, headache, fever,and other adverse effects associated with prior art systemic treatment,is extremely unlikely occur with pepper extracts. In this way, peppercompounds will not add illness to illness, but healing to the patient,without discomfort, or injurious side effects.

Pepper's ability to induce an inflamatory response in the area ofadministration provides an important research tool for studyingimmunostimulation in the treatment of disease. Since inflamationprecipitates a varied array of antifungal serums, including leukocytes,and other mononuclear cells to the site of infection, this antimicrobialeffect is believed to play a major role in pepper's astounding successat curing microbial infections of the keratin layers. These propertiesare valuable in the systemic treatment of disease as well, andparticularly so for immunocomprimised patients.

Perhaps other notably pungent compounds such as those found in garlic,onion, mustard, vanilla, cascarilla, nicotine, lobeline, boneset, etc.,also demonstrate similar therapeutic actions as those found in pepper.It is also probable that nearly all irritants, whether natural, orsynthetic, possess to some degree these same general properties, and aidcure through induction of inflamation.

The role that the active principles in pepper play in the amazinglyrapid healing, and regeneration of tissue injured by burns, lacerations,infections, and disease is also important to immunocomprimised patients,who have particular difficulty in healing, and frequently encounterserious infection from even minor injuries, and diseases. Thesevulnerary actions also play an important role in the treatment ofcancers, and tumors, and other diseases that result in cellularmutation, and abnormal proliferation of tissue.

The astounding effectiveness of pepper compounds to cure dandruff andseborrhea further suggests its regenerative contributions, in additionto its antifungal actions. Though not believed to be of microbialorigin, dandruff and seborrhea are completely cured within a very fewtopical treatments with pepper, as easily as if it were ringworm. Thesehealing and regenerative powers, along with pepper's apparentkeratolytic action, also provides great promise in the treatment of alldiseases that result in an abnormal proliferation of keratin includingscaling conditions such as eczema, psoriasis, general dermatitis, orhardened growths such as warts, corns, and callouses, ect. Theseproperties also make pepper useful in treating cancer, wrinkles, acne,and others disorders.

The discovery of pepper's amazing effectiveness in the treatment ofdandruff and seborrhea, also suggests that other antifungals, includingthose of the prior art, may also demonstrate effectiveness in thetreatment of these, and other forms of dermatitis.

The antimicrobial actions of pepper extracts towards pathogenic fungi,make it an excellent prospect for experimentation with other pathogenssuch as bacteria, in the development of new antiseptics and antibiotics.Pepper's affinity for the skin also makes it a good candidate for thetreatment of staphylococcus, and other bacterial infections of the skin.It's low toxicity also favors its use in the treatment of systemicbacterial infections including all types from ear infections totuberculosis.

Other products utilizing the antimicrobial properties of peppercompounds include clothing, and shoe liners made from capsicum wool, orany other fabric impregnated with pepper compounds as a safeguardagainst harboring these pathogens within one's clothing. For individualswho, for example, have a natural proclivity for contracting athlete'sfoot, socks, or shoes with liners impregnated with pepper may be worn toprevent contamination leading to infection. The same applies toundergarments, and athletic wear, or anything that has contact with theskin, and is a potential contagion of infection.

Pepper offers promise in a wide variety of agricultural applications aswell. Crop fields may be sprayed or dusted with pepper preparations, oradded to irrigation water to facilitate a variety of importantoperation. The antimicrobial properties of pepper will protect the plantfrom fungal, bacterial, and viral disease. It will also protectharvested produce from spoilage. In these two respects, crop yield isincreased, and allowable storage time extended, as microbes take a farless significant tole of the harvested crop.

Pepper's action as an irritant, further serves increased crop yields byperforming as a repellent for crop destroying animals and insects, inaddition to acting as an insecticide. In aerosol form, capsicumpreparations in particular perform like mace, or tear gas, producingextreme burning and irritation of the eyes, nose throat, lungs, and allmucous membranes in amazingly low concentrations. Crops in fieldstreated with capsicum and related plant species will have an intolerablyoffensive taste and odor, that will repel rodents, birds, insects, andmicrobes that otherwise damage crops. Within storage silos, pepperpreparations will act as a preservative by continuing to stem thesedestructive influences, even after delivery to market.

The irritating constituents of pepper are also useful for military andlaw enforcement purposes, as safe alternatives to mace and tear gas, inaddition to their therapeutic, and agricultural uses. When dispersed ina fine mist, or vapor containing an etheral solvent such as alcohol,capsicum pepper in particular produces extreme, and intolerableirritation to the eyes, and respiratory system, along with uncontrolablechoking, and coughing in the most minute dosages! An invisible, andodorless vapor containing a single squirt from a typical fine mistcosmetic bottle containing cayenne pepper ethanol tincture is sufficientto render a fifteen hundred square foot room uninhabitable to humans.Dispersed within tear gas-like canisters, specially suited for thepurpose, very large areas of atmosphere could be covered with very fewdistribution units.

Pepper derivatives, whether used to treat crops, or livestock, areperfect for use in the food industry. Being itself a food compound,generally recognized as safe (GRAS) by the U.S. Food and DrugAdministration, pepper will pose no health risks to consumers of thesefood products. Whether applied topically to livestock, or added to theirfeed, or injected as a systemic antibiotic, pepper derivatives will notraise crucial safety concerns, as all prior art systemics have.

Other possible areas for investigating pepper and its derivativesinclude treatment of trees for Dutch elm disease, and other disorders,and treatment of rare painting and artifacts as a preservative, and asdisinfectant, and as a treatment against parasitic worms.

The list of possible research projects, for the development of newcommercial product derived from the discovery of pepper's absolutelyastonding curative powers, is indeed endless. What new products that areto develop from this discovery is an interesting, and exciting areadeserving of much attention.

The use of pepper compounds in the treatment of tumors, cancer, andother diseases involving cellular mutation of tissue, along with immunedisorders such as AIDS, has excellent prospects for the developement ofmany new drugs, and treatments.

The impact of commercial implementation of this topical antifungaltreatment alone, is to make available to even the poorest people of theworld a certain cure for even the most severe cases of superficialmycoses. A treatment that cures completely in much less time, in a muchsafer way, and for less than one penny on the dollar for what isrequired with prior art treatments. A medication that brings relief tomany millions of sufferers, rich and poor, saves our nation, and eachnation of the world millions of dollars each day in medical costs. Amedicine that provides an important search tool in the treatment of deeptissue mycoses, her life threatening infectious diseases.

While my above description includes many specificities, these should notbe regarded as limitations on the invention, but rather as anexemplification of certain preferred embodiments.

Accordingly, the scope of the invention should not be determined bythese illustrated embodiments, but by the appended claims, and theirlegal equivalents.

I claim:
 1. A method of treating deep tissue, or systemic fungaldiseases comprising:administration to an area of disease a suitablecarrier containing a primary anti-infective agent obtainable fromcapsicum pepper, or an equivalent in a therapeutically effective amount.2. A method of treating systemic fungal diseases selected from the groupconsisting of blastomycosis, coccidioidomycosis, entomophthoromycosis,or paracoccidioidomycosis comprising:administration to an area ofdisease a suitable carrier containing a primary anti-infective agentobtainable from pepper, or an equivalent in a therapeutically effectiveamount.
 3. A method of treating systemic fungal diseases selected fromthe group consisting of aspergillosis, candidiasis, cryptococcosis, orhistoplasmosis comprising:systemic administration to an area of diseasea suitable carrier containing a primary anti-infective agent obtainablefrom pepper, or an equivalent in a therapeutically effective amount. 4.A method of treating fungal infections of the mucosacomprising:administration to an area of disease a suitable carriercontaining a primary anti-infective agent obtainable from a pepper plantof the genus Capsicum, Peperoma, or species Piper retrofractum, Piperlongum, or Piper nigrum in a therapeutically effective amount.
 5. Amethod of treating the superficial manifestations of fungal disease inthe areas of the body about the face, ear, mouth, neck, and below anddeep tissue, or systemic fungal diseases comprising: administration tothe area of disease a suitable carrier containing a primaryanti-infective agent obtainable from pepper, or an equivalent wherein atherapeutically effective amount is a concentration similar to oleoresinor less.
 6. A method of treating the superficial manifestations offungal disease or systemic fungal diseases comprising:administration tothe area of disease a suitable carrier containing a primaryanti-infective agent obtainable from pepper, or an equivalent wherein atherapeutically effective amount is a concentration within the range ofground spice or oleoresin.
 7. A method as in any one of claims 5 or 6,wherein the disease infects the feet.
 8. A method as in any one ofclaims 5 or 6, wherein the disease infects the body area.
 9. A method asin any one of claims 5 or 6, wherein the disease infects the crotcharea.
 10. The method of claim 6, wherein the disease infects the scalp.11. A method as in any one of claims 1-6, wherein the disease iscandidiasis.
 12. A method as in any one of claims 1-6, wherein saidagent is a synthetic.
 13. A method as in any one of claims 2, 3, 5, or6, wherein said pepper is a Capsicum.
 14. A method as in any one ofclaims 1-6, wherein said agent is a capsaicinoid analog.
 15. A method asin any one of claims 2, 3, 5, or 6, wherein said plant is piperaceous.16. A method as in any one of claims 2, 3, 5, or 6, wherein said agentcontains a piperidine constituent.
 17. A method as in any one of claims1-6, wherein said pepper is cayenne.
 18. A method as in any one ofclaims 1-6, wherein said pepper is paprika.
 19. A method as in any oneof claims 1-6, wherein said pepper is black.